Practical Synthesis of a Manβ(1-4)GlcNTroc Fragment via Microfluidic β-Mannosylation

Oligosaccharide Synthesis on Solid, Soluble Polymer, and Tag Supports

“…They have circumvented the problems by using the microfluidic systems and realized the quantitative a-sialylation with perfect a-selectivity, even in a large scale. Significantly, improved glycosylation could be achieved not only for a-sialylation but also for b-mannosylation 40 and N-glycosylation, 104 and the combination of these microfluidic glycosylation [105][106][107] and the solid-supported glycoslylation led to the successful synthesis of complex-type N-glycan with sialic acid as described in Section 16.2.3 (Scheme 16.16).…”

“…38 Two challenging glycosyl bond formations (b-mannosylation and a-sialylation) were constructed in advance in solution-phase or under microfluidic conditions; the synthesis of the fragment c, Manb(1-4)GlcNTroc, was achieved by their highly b-selective mannosylation method, which utilized the trimethylsilyl tetrakis (pentafluorophenyl)borate, TMSB(C 6 F 5 ) 4 , as a Lewis acid/cation trap activator, 39 and by using microfluidic conditions. 40 On the other hand, the quantitative and a-selective sialylation (a : b > 20 : 1) was achieved for the large-scale preparation of the NeuNAca (2-6)Gal disaccharide (fragment d) by using C5-substitued phthalimide or azide imidates through the mechanism of fixed-dipole moment effects under microfluidic conditions (see Section 16.3.4). 41,42 Then, the suitably protected mono-and disaccharide donors (fragments a-d), as the longer storable N-phenyltrifluoroacetimidates, could be stereoselectively glycosylated on JandaJel TM , which was found to be the optimal solid support for glycosylation, with the aid of neighboring group participation.…”

Acid-mediated reactions under microfluidic conditions: A new strategy for practical synthesis of biofunctional natural products

“…Herein, two challenging glycosyl bond formations, i.e., β-mannosylation and α-sialylation, were carried out in advance in solution, by the aid of the microfluidic systems (Fig. 1) [28,31–32]. The problem of the key protecting group manipulation, i.e., the reductive opening of benzylidene acetal group, for the large-scale preparation of the fragment b [30] could also be circumvented under the microfluidic conditions, as will be discussed in the following sections.…”

“…We have been applying these advantageous features of the microfluidic systems to the “key” but “problematic” acid-mediated reactions under the conventional batch apparatus, in practically preparing bioactive natural products [27–33]. Our successful examples are cation-mediated reactions, such as α-sialylation [28,32], β-mannosylation [31], and reductive opening of the benzylidene acetal groups in sugars [30], for which improved procedure under the microfluidic conditions enabled the preparation of key synthetic intermediates for oligosaccharides on a multi-gram scale, eventually leading to a total synthesis of the asparagine-linked oligosaccharide ( N -glycan) [32]. A significant improvement has also been achieved for dehydration, which resulted in the industrial scale-synthesis of the immunostimulating natural terpenoid, pristane, of about 500–1000 kg in a year [29].…”

Synthesis of Fluorinated Glycosyl Amino Acid Building Blocks for MUC1 Cancer Vaccine Candidates by Microreactor-Assisted Glycosylation

“…All these demands are met in continuous flow procedures in microreactor systems. Inspired by already published work concerning the use of microreactors for rapid screenings of glycosylation reactions [30][31][32][33][34][35][36] followed by preparative applications in oligosaccharide syntheses [37], we present now the first examples of glycosyl amino acids as well as fluorinated sugars being glycosylated in a micro-structured reactor (Figure 1). …”